As with the other lines of inquiry reviewed herein, pharmacogenetic studies of naltrexone and OPRM1 are far from conclusive and nonreplications have been reported. Most notably, a large clinical trial did not find support for the moderating effect of Asn40Asp polymorphism on clinical response to naltrexone in a sample of male veterans who were actively involved with Alcoholics Anonymous and intensive psychosocial treatments (Gelernter et al., 2007). In the COMBINE Study, patients who received a more sophisticated psychosocial intervention showed no effect of naltrexone and no OPRM1 pharmacogenetic interaction, suggesting that robust psychosocial interventions may obscure pure pharmacological, as well as pharmacogenetic, effects. Another possible explanation for the discrepancies in clinical trials may be the high likelihood of type II error, especially if naltrexone is not observed to have an overall effect. If one does not observe a pharmacogenetic interaction and there is no main effect of naltrexone, one cannot effectively discriminate between alternative interpretations: one being that there is no effect of OPRM1 variation on naltrexone response and the second being that the study failed to identify a naltrexone
